p53 and retinoblstoma tumor suppressor genes have been shown to be altered in many types of human cancer. In addition, in model systems, the combination of a p53 and a ras activating mutation have been required for tumorigenic conversion. We have analyzed a panel of human mesothelioma cell lines for alterations in these genes. In 20 cell lines from 17 individuals, 2 had p53 point mutations and one was a p53 null cell. No Ki-ras activating mutations were detected in any of the 20 cell lines. These studies showed that p53 expression was detectable by immunocytochemistry in normal human pleural mesothelial cells as well as 12 mesothelioma cell lines. The expression level of the human MDM2 gene in mesothelioma cell lines is being investigated since this gene product is frequently found to associate with the p53 protein and is amplified in some tumors in which p53 gene alterations are undetectable. Retinoblastoma gene mRNA expression appeared to be normal and protein studies are ongoing. A ribonuclease protection assay to allow quantitation of mRNA levels for PDGF receptor alpha and beta genes has been developed. This will be applied to human mesothelial cells and mesotheliomas as well as to T antigen immortalized human mesothelial cells overexpressing PDGF-A chain genes and appropriate control cells.